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Researchers Study Genetic Regions in Mice to Find How We Might Resist Plague
Friday, October 21st, 2016

Black Death

Plague at Ashdod 1630, Nicolas Poussin

During the height of the Black Death, millions of people died of bubonic plague, but some survived infection. Why did they survive, and what can that teach us about surviving future epidemics?

A team at the University of Illinois College of Medicine at Urbana-Champaign recently examined how specific strains of mice resist infection to bubonic plague bacteria, and has attempted to trace that resistance to a single genetic region.

The study, led by medical student Mike Tencati and U. of I. microbiology professor Dr. Richard Tapping, is reported in the October issue of the journal Infection and Immunity.

Tencati, an M.D./Ph.D. candidate at the Urbana campus of the University of Illinois, said researchers are not necessarily looking for a cure for Yersinia pestis, or bubonic plague bacteria. Rather, the study focuses on the reaction in the host (mice) exposed to the bacteria in an attempt to determine what is genetically similar among those who resist infection. Their study, Tapping said, in a broad sense, is trying to better understand how humans could fight off other infectious diseases.

“You have microbes, and they’re trying to do everything to win the battle,” Tencati said, “and we have us, trying to do everything to make sure they don’t wipe us out.”

According to Tapping, Yersinia pestis is a highly studied pathogen in terms of its virulence factors, but few studies concentrate on the genetic determinants in the host that contribute to fighting bubonic plague bacteria. Working with mammals is harder because it can be difficult to see how they adapt as a host, Tencati said, when microbes are much easier to manipulate. Tapping and Tencati’s study, which used a non-contagious and less virulent strain of bubonic plague bacteria, attempted to find specific genes on chromosome 1 in mice that might be contributing to resistance. Although unable to narrow down to a single genetic region in this particular study, Tapping and Tencati said, their findings did identify a strong genetic locus on chromosome 1 and found evidence that suggests resistance in their particular strain of mice, known as 129, occurs in the early stages of the infection.

“We know this effect happens early on, so we were thinking it might be something to do with early responder cells to infection,” Tencati said.  

Bubonic plague is actually treatable if caught early, Tapping said. A few cases occur in regions of India and China, and some in the southwestern U.S., only about 20 cases a year. From the perspective of bioterrorism, the concern is if bubonic plague transitions into pneumonic plague, Tapping said, which has a more rapid rate of infection, higher mortality rate and spreads quickly from person to person through coughing. Research on bubonic plague bacteria can help answer questions about the types of defenses a human could mount against bubonic plague, he said, if there is anything — like a vaccine — that could enhance that protective response. 

“When people immediately think of plague, they think of the Black Death,” Tapping said. “It’s thought to have decimated up to 50 percent of the European population. Obviously when you’re faced with that history, there’s concern with ‘Hey could this happen again?’ We’ve gone a long time without an epidemic of that proportion, but there are certain parts of the world that still have outbreaks of plague.”

Undergraduate students at Illinois, many who study in the School of Molecular and Cellular Biology, assisted the research by maintaining the mice populations, analyzing genetic markers and working with physical manipulations of the DNA. Tapping’s graduate students often move on to pursue a combination of clinical and research work, medical residencies, vaccine research or academia. Tencati, for instance, is in his second year of medical school and plans to finish his M.D./Ph.D. by 2019.

Tapping, who has been conducting research at Illinois for the last 15 years, said he focuses mainly on innate immunity sensing, in particular, groups of receptors that are the body’s earliest defense mechanism against disease.

Conducting research using bubonic plague bacteria — by looking at genetic resistance in mice —contributes toward better understanding of host-pathogen interactions, he said.

“When we identify these individual genes, it’s is important in terms of conferring resistance and a better understanding of host responses in dealing with infection.”

Tencati and Tapping’s paper, “Genetic Mapping of Plague Resistance of 129 Mice,” is available from the journal Infection and Immunity.

Author: Meaghan Downs

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